A urinary isolate of *Enterococcus faecalis* carries a plasmid‑mediated *vanA* gene. (a) Describe how the *vanA* gene confers resistance to vancomycin. (b) Recommend an oral antibiotic that would likely be effective against this strain and justify your choice based on its mechanism of action and the resistance profile.
Answer
(a) *vanA* encodes enzymes that remodel the peptidoglycan precursor from D‑Ala‑D‑Ala to D‑Ala‑D‑Lac, reducing vancomycin binding affinity by ~1,000‑fold, thus conferring high‑level resistance. (b) Linezolid, an oral oxazolidinone that inhibits the initiation of bacterial protein synthesis by binding to the 50S ribosomal subunit, is effective because its target is unrelated to cell‑wall synthesis and *vanA* does not affect its action.
Step-by-step solution
- State that vancomycin normally binds to the D‑Ala‑D‑Ala terminus of the nascent peptidoglycan chain, blocking transglycosylation and transpeptidation.
- Explain that the *vanA* operon produces a ligase that substitutes the terminal D‑Ala with D‑Lac, creating D‑Ala‑D‑Lac termini.
- Note that the change removes a critical hydrogen‑bond donor, decreasing vancomycin binding affinity by about 1,000‑fold, which leads to high‑level resistance.
- Identify an oral agent whose mechanism does not involve cell‑wall synthesis; linezolid fits because it blocks the formation of the initiation complex on the 50S ribosomal subunit.
- Justify linezolid’s use: it is active against VRE, is orally bioavailable, and resistance to *vanA* does not impact its protein‑synthesis inhibition.
Common mistake: Assuming vancomycin resistance also protects against all cell‑wall active agents
Concept tested: Vancomycin resistance via *vanA* and alternative therapy
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